A Phase I Study of Romidepsin, Gemcitabine, Dexamethasone and Cisplatin Combination Therapy in the Treatment of Peripheral T-Cell and Diffuse Large B-Cell Lymphoma
- Patients with histologically confirmed PTCL. Biopsy proof of disease at initial
diagnosis is mandatory. A biopsy at relapse is preferred but not mandatory.
- Patients must have received one or two previous regimens of therapy for their disease
(salvage chemotherapy plus autologous stem cell transplantation is considered to be
- Clinically and / or radiologically measurable disease (1 site bidimensionally
measurable). Measurements / evaluations must be done within 28 days prior to
- Age 18 to 75 years.
- ECOG performance status 0, 1 or 2.
- Life expectancy of ≥ 90 days (3 months).
- Laboratory Requirements: (must be done within 7 days of registration)
- Granulocytes (AGC) ≥ 1.0 x 10^9/L
- Platelets ≥ 75 x 10^9/L (≥ 50 if bone marrow involvement by lymphoma)
- AST and ALT ≤ 2.5x ULN (≤ 5x ULN if hepatic involvement of disease)
- Serum total bilirubin ≤ 1.5x ULN (≤ 3x ULN if hepatic involvement of disease, or ≤5x
ULN if Gilberts Disease)
- Serum Potassium ≥ 3.8 mmol/L*
- Serum Magnesium ≥ 0.85 mmol/L* * NB: Patients with potassium and magnesium levels
below these values are eligible if supplementation has corrected these deficits. This
supplementation should continue throughout the course of the study.
- Calculated creatinine clearance (Cockcroft-Gault formula) of ≥ 50 mL /min.
- Women must be post-menopausal, surgically sterile or use reliable forms of
contraception while on study and for 90 days after discontinuing therapy. Women
of childbearing potential must have a pregnancy test taken and proven negative
within 7 days prior to registration and must not be lactating.
- Patient consent must be obtained according to local Institutional and/or
University Human Experimentation Committee requirements.
- Patients must be accessible for treatment and follow-up. Patients registered on
this trial must be treated and followed at the participating centre. This
implies there must be reasonable geographical limits (for example: 1 ½ hour's
driving distance) placed on patients being considered for this trial.
- In accordance with NCIC CTG policy, protocol treatment is to begin within 2
working days of patient registration.
- Patients with a history of other malignancies, except: adequately treated
non-melanoma skin cancer and superficial bladder cancer, curatively treated in-situ
cancer of the cervix or breast, or other solid tumours curatively treated with no
evidence of disease for ≥ 5 years.
- Central nervous system involvement, meningeal or parenchymal. Patients with CNS
disease at initial presentation and who are in a CNS CR at the time of relapse are
eligible. MRI scanning and / or lumbar puncture should be performed if there is
clinical suspicion of active CNS disease.
- HIV, active hepatitis B or current hepatitis C infection. (Hepatitis B core antibody
positive, surface antigen negative patients allowed if concurrent anti-viral
prophylaxis is administered. Patients with a past history of hepatitis C who have
eradicated the virus are eligible.)
- Any serious active disease or co-morbid medical condition, laboratory abnormality, or
psychiatric illness that would prevent the patient from participating (according to
- Patients with serious cardiac illness or condition including, but not limited to:
- history of documented congestive heart failure (CHF)
- systolic dysfunction (LVEF < 45% by MUGA or ECHO)
- high risk uncontrolled arrhythmias (ventricular tachycardia, high-grade
AV-block, supraventricular arrhythmias which are not adequately rate-controlled)
- unstable angina pectoris requiring anti-anginal medication
- clinically significant valvular heart disease
- evidence of transmural infarction on ECG
- New York Heart Association (NYHA) Class III or IV functional status
- patients with congenital long QT syndrome, history of significant cardiovascular
disease and/or taking drugs leading to significant QT prolongation
- patients with QTc > 480 msec are not eligible
- Pregnant or lactating females or women of childbearing potential not willing to use
an adequate method of birth control for the duration of the study.
- Patients with active or uncontrolled infections, or with serious illnesses or medical
conditions which would not permit the patient to be managed according to the protocol
are not eligible.
- Patients are not eligible if they have a known hypersensitivity to the study drugs or